LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer

Liu, Meiyuan; Cai, Rui; Xia, Yang; Wang, Meng; Zhongsheng, Kuang; Xie, Yuhui; Zhang, Jiren; Zheng, Yanfang

doi:10.21037/atm-21-4507

Cited by 16 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…LUAD samples were also characterized by a higher percentage of LAMC2 (4.97% vs 1.79%) and CXCL1 cells (16.95% vs 12.5%). As CXCL1 and LAMC2 are associated with recruitment of neutrophils and macrophages into tumor tissue 23,24 , these results demonstrate the significant role of immune cell population in LUAD growth. In contrast to LUAD, LUSC samples were more abundant in CDKN2A (14.65% vs 1.05%), proliferating (26.33% vs 1.73%), and SOX2 cancer cells (43.89% vs 24.18%).…”

Section: Resultsmentioning

confidence: 66%

An integrated single-cell transcriptomic dataset for non-small cell lung cancer

Prazanowska

Lim

2023

Sci Data

View full text Add to dashboard Cite

As single-cell RNA sequencing (scRNA-seq) has emerged as a great tool for studying cellular heterogeneity within the past decade, the number of available scRNA-seq datasets also rapidly increased. However, reuse of such data is often problematic due to a small cohort size, limited cell types, and insufficient information on cell type classification. Here, we present a large integrated scRNA-seq dataset containing 224,611 cells from human primary non-small cell lung cancer (NSCLC) tumors. Using publicly available resources, we pre-processed and integrated seven independent scRNA-seq datasets using an anchor-based approach, with five datasets utilized as reference and the remaining two, as validation. We created two levels of annotation based on cell type-specific markers conserved across the datasets. To demonstrate usability of the integrated dataset, we created annotation predictions for the two validation datasets using our integrated reference. Additionally, we conducted a trajectory analysis on subsets of T cells and lung cancer cells. This integrated data may serve as a resource for studying NSCLC transcriptome at the single cell level.

show abstract

Section: Resultsmentioning

confidence: 66%

An integrated single-cell transcriptomic dataset for non-small cell lung cancer

Prazanowska

Lim

2023

Sci Data

View full text Add to dashboard Cite

show abstract

“…LAMC2 (laminin gamma 2 chain) has been reported to be involved in the malignant behavior of OSCC by targeting relevant miRNAs and lncRNAs [ 15 , 29 , 30 ]. Furthermore, LAMC2 expression is positively associated with macrophage infiltration in lung cancer [ 21 ]. LAMC2, via exosomal miR-146a, mediates increased chemotherapy sensitivity of ovarian cancer cells through the PI3K/AKT pathway [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…We have observed that both sEVs and M2 macrophages exert their biological functions via the PI3K/AKT signaling pathway in various cancers [ 16 – 20 ]. Furthermore, recent reports have shown that LAMC2 induces the infiltration of macrophages in lung cancer [ 21 ] and that sEVs transfer a miRNA in ovarian cancer via a LAMC2-mediated PI3K/AKT axis [ 22 ]. On the basis of previous studies, we hypothesized that OSCC-CSC-derived sEVs (OSCC-CSC-sEVs) might transfer a ceRNA of miR-134, thereby promoting M2 macrophage polarization by targeting LAMC2 via the PI3K/AKT signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

Oral Cancer Stem Cell-Derived Small Extracellular Vesicles Promote M2 Macrophage Polarization and Suppress CD4+ T-Cell Activity by Transferring UCA1 and Targeting LAMC2

Yao

et al. 2022

Stem Cells International

View full text Add to dashboard Cite

Cancer-derived small extracellular vesicles (sEVs) are emerging as crucial mediators of intercellular communication between cancer cells and M2-tumor-associated macrophages (M2-TAMs) via transferring lncRNAs. We previously reported that miR-134 blocks the expression of its targeting protein LAMC2 via the PI3K/AKT pathway and inhibits cancer stem cell (CSC) migration and invasion in oral squamous cell carcinoma (OSCC). This study hypothesize that OSCC-CSC-derived small extracellular vesicles (OSCC-CSC-sEVs) transfer a ceRNA of miR-134 and consequently promote M2 macrophage polarization by targeting LAMC2 via the PI3K/AKT pathway through in vitro and in vivo experiment methods. The results showed that sEVs derived from CD133+CD44+ OSCC cells promoted M2 polarization of macrophages by detecting several M2 macrophage markers (CD163, IL-10, Arg-1, and CD206+CD11b+). Mechanistically, we revealed that the lncRNA UCA1, by binding to miR-134, modulated the PI3K/AKT pathway in macrophages via targeting LAMC2. Importantly, OSCC-CSC-sEV transfer of UCA1, by targeting LAMC2, promoted M2 macrophage polarization and inhibited CD4+ T-cell proliferation and IFN-γ production in vitro and in vivo. Functionally, we demonstrated that M2-TAMs, by transferring exosomal UCA and consequently targeting LAMC2, enhanced cell migration and invasion of OSCC in vitro and the tumorigenicity of OSCC xenograft in nude mice. In conclusion, our results indicated that OSCC-CSC-sEV transfer of UCA1 promotes M2 macrophage polarization via a LAMC2-mediated PI3K/AKT axis, thus facilitating tumor progression and immunosuppression. Our findings provide a new understanding of OSCC-CSC molecular mechanisms and suggest a potential therapeutic strategy for OSCC through targeting CSC-sEVs and M2-TAMs.

show abstract

“…The LAMC2 expression was significantly upregulated in colorectal cancer tissues compared with adjacent normal tissues, and high LAMC2 expression is known to be associated with poor patient prognosis 6. Furthermore, overexpression of LAMC2 has been reported in pancreatic ductal adenocarcinoma,7–11 non-small cell lung cancer,12 penile squamous cell carcinoma,13 ovarian cancer,14 oral tongue squamous cell carcinoma,15 cholangiocarcinoma16 and oesophageal squamous cell carcinoma,17 leading to poor clinicopathological features and short survival time.…”

Section: Introductionmentioning

confidence: 99%

LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis

Liu

Xie

et al. 2022

BMJ Open

View full text Add to dashboard Cite

ObjectivesAccumulating evidence suggested that the laminin γ2 (LAMC2) expression level was upregulated in various cancers. However, the potential prognostic value of LAMC2 in cancers remains unclear. We conducted a meta-analysis to clarify the association of LAMC2 expression with prognosis.DesignWe searched Embase, Web of Science and PubMed (up to 25 November 2021) to collect all eligible studies, and meta-analysis was performed to interpret the association of LAMC2 expression with clinicopathological parameters, overall survival (OS), disease-specific survival (DSS) and progression-free survival (PFS).Eligibility criteria for including studiesWe included studies that investigate the relationship between LAMC2 and prognosis of cancers, patients were divided into two groups, and associations of LAMC2 expression with clinicopathological features were described.ResultsSeven studies were finally included. We found that increased LAMC2 expression was significantly associated with lymph node metastasis (log OR 0.88, 95% CI 0.38 to 1.38, p<0.001), tumour-node-metastasis stages (log OR: 0.95, 95% CI 0.39 to 1.50, p<0.001) and tumour status (log OR 1.26, 95% CI 0.84 to 1.68, p<0.001), but not with age (log OR −0.05, 95% CI −0.37 to 0.27, p=0.75) or gender (log OR −0.07, 95% CI −0.52 to 0.38, p=0.75). In addition, higher LAMC2 expression was found to be significantly associated with OS/PFS/DSS (HR 1.85, 95% CI 1.31 to 2.40, p<0.001). A similar result was found in The Cancer Genome Atlas database. High LAMC2 expression was significantly associated with OS in lung adenocarcinoma, mesothelioma, skin cutaneous melanoma, neck squamous cell carcinoma and brain lower grade glioma.ConclusionOur results suggested that higher LAMC2 expression was correlated with worse survival, lymph node metastasis, tumour-node-metastasis stages and tumour status. This study was subject to inherent limitations, but the results presented here provide insights regarding the potential use of LAMC2 as a biomarker for human cancer.Study registrationresearchregistry.com (researchregistry1319).

show abstract

LAMC2 promotes the proliferation of cancer cells and induce infiltration of macrophages in non-small cell lung cancer

Cited by 16 publications

References 29 publications

An integrated single-cell transcriptomic dataset for non-small cell lung cancer

An integrated single-cell transcriptomic dataset for non-small cell lung cancer

Oral Cancer Stem Cell-Derived Small Extracellular Vesicles Promote M2 Macrophage Polarization and Suppress CD4+ T-Cell Activity by Transferring UCA1 and Targeting LAMC2

LAMC2 as a prognostic biomarker in human cancer: a systematic review and meta-analysis

Contact Info

Product

Resources

About